1. Technical Field
The present invention pertains to the microfluidic manipulation technology, and more particularly relates to a digital microfluidic manipulation device capable of simultaneously manipulating a plurality of microdroplets and the manipulation method thereof.
2. Description of the Prior Art
Manipulation of fluid is an essential technique for microfluidic biochips, and is mainly related to manipulation of continuous fluid and non-continuous fluid (droplet base). Compared with the continuous fluid, the non-continuous fluid is easier to be manipulated. Moreover, a smaller volume of fluid sample is required for the manipulation of non-continuous fluid, hence it requires less cost and takes shorter time. In recent years, non-continuous fluid manipulation techniques focusing on droplets manipulation develop very fast, and have been gradually applied to every technical field, especially biochemical and medical field. For biochemical and medical detection, a fluid manipulation technique of high efficiency, high throughput, limited pollution and low cost is particular suitable for the purposes of sequencing DNA, detecting protein, monitoring environmental pollution factors, developing new drugs and releasing pharmaceutical gradient. Therefore, the current development of droplet manipulation technique places great emphasis on developing a device and method featuring excellent manipulability and high biological compatibility and exempted from interference with fluid samples.
The driving force for microdroplet mainly comes from changes of free energy gradient of the droplet on the surface, thus open type microfluidic system (i.e. digital microfluidic system) is greatly influenced by the surface tension of the microdroplets. If the microdroplet has a variation in the free energy of the left portion and the right portion of the surface thereof, the microdroplet will move after overcoming the energy barrier. The variation in the free energy of the microdroplet can be achieved by properly designing the surface structure of the microfluidic manipulation system. Thus the design of the surface structure and the improvement of throughput for microfluidic manipulation system are important issues in driving the microdroplet to move.
In currently developed minute elements, most of the microdroplets merely show limited wettability on a surface having unitary structural density. At present, many researches have been conducted to study the influence of changes in surface structure density on the hydrophobicity of the microdroplets. Many scholars and research teams have already proposed various approaches that alter the surface tension gradient of the microdroplets through altering the structural density of the surface to manipulate the microdroplets thereon. Several approaches using thermal energy, optical energy, electricity (e.g. electro-wetting-on-dielectric, EWOD) and surface density gradient to drive microfluidic have been demonstrated.
However, those driving approaches using thermal energy, optical energy, and electricity require expensive equipments and precise control to realize the manipulation of droplets. Another serious drawback is that the application of external energy may cause deterioration of substances in the droplet or other adverse effects. For instance, thermal energy may increase the speed of evaporation of the droplet, or electricity field may pose protein or DNA adsorption on the structural surface, thereby rendering it impossible to manipulate the droplet. These drawbacks not only affect the results of detection but also restrict the range of application of these approaches.
Alternatively, the surface treated with chemical or biological modifications (e.g. self-assembled monolayer, SAM) can be used to drive microdroplets without external energy. Nevertheless, the manipulability of such approach is poor. Droplets usually move along a given route and could not be manipulated two-dimensionally.
Another known method is to utilize a stretchable elastic surface with nano- or micro-composite structures to control structural densities and to generate wettability gradients. This method requires a microdroplet manipulation device comprising an elastic substrate with nano-composite or micro-composite structures and a control unit. The control unit stretches the elastic substrate to alter the structural density of the nano-composite or micro-composite structures and thereby to manipulate droplets. This method can achieve biological compatibility. However, this method also requires expansive equipments and precise control to realize the manipulation of droplets. Furthermore, the droplets could only move in a single direction on the textured surface at the same time. Moreover, it is not easy to integrate the stretchable elastic surface with other devices since their external control systems are not compact.
In “A wettability switchable surface by microscale surface morphology change”, J. Micromechanics and Microengineering, 17(2007), 489-495, Chen et al. provide a device that utilizes an electrostatic force to control the structural density of nano-composite or micro-composite structures so as to control droplets. However, the device requires an additional ground electrode to prevent bio-ingredients of droplets from being interfered by a driving energy.
In order to address these issues, this invention proposes a method and a platform capable of simultaneously and precisely delivering multi-droplets to react at a high throughput rate. Furthermore, droplets can be manipulated using a suction force, hence avoiding interference from a driving energy (e.g. optical energy, electricity, or heat energy). This platform can also be easily integrated with other devices and can achieve high bio-compatibility. Hence, this platform has a great potential for digital fluidic systems in bio-applications.